Tenth Case of Bilateral Hemifacial Spasm Treated by Microvascular

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Review Article Tenth case of bilateral hemifacial spasm treated by microvascular decompression: Review of the pathophysiology Warley Carvalho da Silva Martins1, Lucas Alverne Freitas de Albuquerque1, Gervásio Teles Cardoso de Carvalho1,2, Jules Carlos Dourado1, Marcos Dellaretti1,2,3, Atos Alves de Sousa1

1Department of Neurosurgery, Hospital Santa Casa de Belo Horizonte, 2Faculty of Medical Sciences of Minas Gerais, 3Department of Neurosurgery, Hospital das Clínicas de Belo Horizonte, Belo Horizonte, Minas Gerais, Brazil

E‑mail: *Warley Carvalho da Silva Martins - [email protected]; Lucas Alverne Freitas de Albuquerque - [email protected]; Gervásio Teles Cardoso de Carvalho - [email protected]; Jules Carlos Dourado - [email protected]; Marcos Dellaretti - [email protected]; Atos Alves de Sousa ‑ [email protected] *Corresponding author

Received: 04 March 17 Accepted: 20 April 17 Published: 26 September 17

Abstract Background: Bilateral hemifacial spasm (BHFS) is a rare neurological syndrome whose diagnosis depends on excluding other facial dyskinesias. We present a case of BHFS along with a literature review. Methods: A 64‑year‑old white, hypertense male reported involuntary left hemiface contractions in 2001 (aged 50). In 2007, right hemifacial symptoms appeared, without spasm remission during sleep. Botulinum toxin type A application produced partial temporary improvement. Left microvascular decompression (MVD) was performed in August 2013, followed by right MVD in May 2014, with excellent results. Follow‑up in March 2016 showed complete cessation of spasms without medication. Results: The literature confirms nine BHFS cases bilaterally treated by MVD, a definitive surgical option with minimal complications. Regarding HFS pathophysiology, ectopic firing and ephaptic transmissions originate in the root Access this article online exit zone (REZ) of the facial nerve, due to neurovascular compression (NVC), Website: orthodromically stimulate facial muscles and antidromically stimulate the facial nerve www.surgicalneurologyint.com DOI: nucleus; this hyperexcitation continuously stimulates the facial muscles. These 10.4103/sni.sni_95_17 activated muscles can trigger somatosensory afferent skin nerve impulses and Quick Response Code: neuromuscular spindles from the trigeminal nerve, which, after transiting the Gasser ganglion and trigeminal nucleus, reach the somatosensory medial posterior ventral nucleus of the contralateral thalamus as well as the somatosensory cortical area of the face. Once activated, this area can stimulate the motor and supplementary motor areas (extrapyramidal and basal ganglia system), activating the motoneurons of the facial nerve nucleus and peripherally stimulating the facial muscles.

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How to cite this article: da Silva Martins WC, de Albuquerque LA, de Carvalho GT, Dourado JC, Dellaretti M, de Sousa AA. Tenth case of bilateral hemifacial spasm treated by microvascular decompression: Review of the pathophysiology. Surg Neurol Int 2017;8:225. http://surgicalneurologyint.com/Tenth-case-of-bilateral-hemifacial-spasm-treated-by-microvascular-decompression:-Review-of-the-pathophysiology/

Conclusions: We believe that bilateral MVD is the best approach in cases of BHFS. Key Words: Bilateral hemifacial spasm, botulinum toxin, microvascular decompression

INTRODUCTION remained. In May 2014, he was submitted to right MVD, again presenting moderate postoperative peripheral facial Hemifacial spasm (HFS) is a common, involuntary, paresis, with full recovery in 3 weeks. All right HFS intermittent movement disorder induced in most ceased, but the previous right hypoacusis remained. cases by neurovascular compression (NVC) in the root He remained free from facial spasms until August 2014, exit zone (REZ) of the ipsilateral facial nerve in the when he began to experience mild relapse in the right brainstem.[5,19,92,94] Bilateral involvement of the face is a hemiface, with two to three fleeting spasms of the very rare event, ranging from 0.6 to 5% of cases of facial orbicularis muscle per hour and no episodes during sleep, spasm.[17,19,57,81,93,94] which had previously been an important complaint. His To our knowledge, this is the tenth case of bilateral HFS health status remained the same during 19 months of (BHFS) treated by microvascular decompression (MVD) follow‑up. In March 2016, he returned for evaluation to be described. A comprehensive review of the literature showing cessation of spasms without medication. The follows the case report. hearing deficits did not improve.

MATERIALS AND METHODS/CASE RESULTS AND DISCUSSION MATERIAL Epidemiology Case report The annual incidence of HFS is 0.81 per 100,000 in A 64‑year‑old, white, hypertense male reported the onset women and 0.74 per 100,000 in men. The average of involuntary contractions of the left orbicularis muscle prevalence is 11 per 100,000 in the general population. in 2001 (aged 50), which progressed to contractions Women develop the disease in 14.5 per 100,000 of all the muscles in this hemiface. In 2007, symptoms individuals and men in 7.4 per 100,000 individuals, thus also appeared in the right orbicularis muscle and again female:male distribution is 2:1.[3,4,93] Prevalence increases progressed to all muscles in this hemiface. The patient with age, affecting 37.9 per 100,000 inhabitants in those reported no remission of spasms in either hemiface during over 70 years old.[73] sleep. Carbamazepine was prescribed (200 mg BID) with A systematic review of 5,685 cases of HFS submitted slight improvement in the symptoms initially, followed to MVD showed 69% were female and 31% were male. by relapses. Next, he was submitted to applications of Patient mean age at surgery was 54 (45–58) years old. The botulinum toxin type A (BTX‑A), which produced partial mean duration of symptoms was 6.5 (4.2–10.7) years.[63] temporary improvement. Among 6,029 patients with HFS submitted to MVD, The course of the disease included bilateral progressive 66.82% were female and 33.18% were male [Table 1]. hearing loss. In September 2012, he was submitted Comparisons between patients submitted to MVD and to audiometry, which showed mild to moderate those treated with BTX‑A showed they were similar in age, sensorineural loss (descending audiometric curve) in but the latter had a lower mean disease duration (6.7 vs. both ears. Magnetic resonance imaging (MRI) was 4.3 years, respectively).[93] performed in October 2012 and showed that the left vertebral artery followed a tortuous and elongated path, Cases of bilateral hemifacial spasm in the compressing and dislocating ipsilateral cranial nerves VII literature and VIII, compatible with neurovascular conflict, and To our knowledge, only 102 cases of BHFS have been discrete tortuosity of the right posterior inferior cerebellar reported [Table 2],[6,13,19,31,47,55‑57,72,81,86,92,94,100,105] and of artery (PICA), touching the brainstem along the REZ of these, only 10 cases were submitted to bilateral MVD, the VII‑VIII nerve complex on the right side. including our case.[6,13,81] The patient was submitted to left MVD in August 2013 In cases of BHFS, following a highly variable latency because the symptoms were more pronounced in this period of approximately 33–100 months, the spasms, hemiface. He evolved with complete cessation of spasms which initially begin in one hemiface, progress to the in the left hemiface, presenting moderate postoperative contralateral side.[55,94] In our case, the interval was peripheral facial paresis with progressive and full 6 years (72 months). The patient then goes on to present improvement in December, though the left hypoacusis involuntary painless asymmetric asynchronous facial Surgical Neurology International 2017, 8:225 http://www.surgicalneurologyint.com/content/8/1/225

Table 1: Epidemiology of patients with HFS Authors and year (location) Number of Females/ Left/right Mean age/years Mean duration of symptoms HFS/MVD Male (%) sides (%) until treatment/years Huang et al., 1992 (Taipei, Taiwan) 310 46/54 54.2/45.8 53.4 ‑ Barker et al., 1995 (Pittsburgh, USA) 648 65/35 60/40 52 8 Zhang et al., 1995 (Guangzhou, China) 300 56.3/43.7 44.7/55.3 ‑ 6 Payner and Tew, 1996 (Cincinnati, USA) 34 55.9/44.1 52.9/47.1 52 6.8 Ishikawa et al., 2001 (Saitama, Japan) 175 62.9/37.1 57.7/42.5 53 6.8 Samii et al., 2002 (Hannover, Germany) 143 62.2/37.8 56.6/43.4 54.5 6 Li, 2005 (Taipei, Taiwan) 545 ‑ 59.8/40.2 54.8 5.4 Yuan et al., 2005 (Beijing, China) 1,200 59.6/40.4 45.3/54.7 53 ? Han et al., 2009 (Sungnam, Korea) 1,642 77.3/22.7 ‑ 49.5 (3.4 <30 yrs) 7 Hyun et al., 2010 (Seoul, Korea) 1,174 71.1/28.9 50.2/49.8 48.8 5.6 Thirumala et al., 2011 (Pittsburgh, USA) 293 64.8/35.2 56/44 52.25 ‑ Rosenstengel et al., 2012 (Greifswald, 110 62.7/37.3 64.45/34.55 ‑ 8.1 Germany) Total or percentage (%) 6,574 66.82/33.18 52.43/47.57 ‑ Variations from 5.4 to (in 6,029) (in 4,932) 8.1 years: mean 6.7 years Miller and Miller, 2012 (North Carolina, 5,685 69/31 ‑ 54 6.5 USA) Systematic Review Tan et al., 2004 (Singapore) BTX‑A 80 67.5/32.5 ‑ 56.3 4.3

Table 2 (Part I): The 102 cases of bilateral HFS Authors and Ehni and Gardner Eckman, Kramer Møller and Holds et al.*, Niemeyer Van de Rosso et al., year (location) Woltman, and Dohn, and Altrocchi, Møller, 1990 (USA) Filho, Biezenbos 1994 (Brazil) 1945 (USA) 1966 (USA) 1971 (USA) 1985 (USA) Bezerra and et al., 1992 Mufarrej, (Netherlands) 1990 (Brazil) Age at onset n/a 68 41 n/a 62 n/a 24 45 (Years) Sex 5F, 1M 1F 1M 1 F *1F 1 ? 1F 1F % BHS 5.7 n/a n/a 0.7 n/a 1.9 n/a n/a Etiology n/a Paget’s Vascular Vascular Vascular Vascular MS Vascular Comorbidity n/a n/a Bilateral HI n/a n/a n/a BP None Side of onset n/a R L L R n/a L L Duration/years n/a 5 14 n/a 14 n/a 2 >2 Latency <1-15 yrs 7 mos 14 yrs 2 yrs ~11 yrs n/a 1 mo 6 mos (between R and L sides) Neuroimaging n/a n/a Tortuosity on right n/a Vertebrobasilar Internal MS Normal diagnosis VA dolichoectasia R auditory CT and artery angiography Therapy n/a n/a Diphenylhydantoin L: MVD (1980) R: MVD (1978, MVD TXP and MTP L: MVD (PICA R: MVD (1982) 1979, 1980) and AICA) Myectomy (1984) R: MVD L: CsT. (AICA) Result n/a n/a n/a n/a R: recurrence Excellent TXP: no L: transient (1979, 1980, 1982) response BP, mild HI, 1984: MI MTP: no nystagmus 1987: anacusis response in BHS R: transient L: ? after 10 days BP, HI Follow‑up n/a n/a n/a n/a 108 mos 12 mos 2 mos 3 mos *: Concomitance case, n/a: not available, AD: Antidepressant, AED: Antiepileptic drug, AICA: Anterior inferior cerebellar artery. MRI: Magnetic resonance imaging. BA: basilar artery. BHS: Bilateral hemifacial spasm, BP: Bell’s paralysis, BTX: Botulinum toxin injections, BZD: Benzodiazepine, CBZ: Carbamazepine, C‑dopa: Carbidopamine, CNZ: Clonazepam, CsT: Conservative treatment, CT: Computed tomographic, F: Female, HBP: Hypertension blood pressure, HI: Hearing impairment, M: Male, MI: Marked improvement, MS: Multiple sclerosis, MTP: Methylprednisolone, MVD: microvascular decompression, PICA: Posterior inferior cerebellar artery, SA: Small arteries. SAV: Small arteries and veins, TN: Trigeminal neuralgia, TXP: Trihexyphenidyl. VA: Vertebral artery, ~: Mean Surgical Neurology International 2017, 8:225 http://www.surgicalneurologyint.com/content/8/1/225

Table 2 (Part II): The 102 cases of bilateral HFS Authors and Barker Schulze‑Bonhage Tan and Jankovic, Llaves‑Estévez Machado Tan and Katz et al., year (location) et al.*, and Ferbert, 1999 (USA) et al., 2002 et al., 2003 Chan, 2004 2007 (USA) 1995 (USA) 1998 (Germany) (Spain) (Brazil) (Singapore) Age at n/a 60 70.6 (average) 66.7 (average) 70 56 (average) 66 onset (years) Sex 8 ‑*1=7? 1M 4F, 1M 8F 1M 1F, 1M 1? % BHS 1.2 n/a 3.2 n/a n/a 1.6 n/a Etiology Vascular Vascular Vascular (3 cases) n/a Vascular Vascular Vascular Comorbidity n/a n/a TN 4 BP, n/a HBP Blefarospasm 1 neuroborreliosis Side of onset n/a L 5 L 4 L, 4 R R 2 L L Duration/years n/a n/a 17 (mean) 10 (mean) 15 4 (mean) 6 Latency n/a n/a 8.4 yrs (mean) 54 mos (mean) 14 yrs 1.5 yrs (mean) 3 yrs (between R and L sides) Neuroimaging PICA >AICA Elongated VA and 3 Vertebrobasilar n/a MRI: VA and 1 Vertebral and R: VA + PICA/L: diagnosis or VA>SAV BA arteries, 1 Normal BA tortuosity 2 AICA Dolichoectatic VA >SA image, 1? Therapy 3 bilateral L: MVD 5 BTX, 2CNZ, 7 BTX BTX, CBZ, CNZ 2 BTX Tramadol e MVD R: CsT 1 CBZ, and 1 L‑dopa/C‑dopa, MVD (L) bilateral with BTX Result n/a L: transient BP n/a n/a n/a n/a n/a and HI Follow‑up n/a 4 mos 5 mos, 3 mos, n/a, 118 mos n/a n/a n/a 6 mos, n/a *: Concomitance case, n/a: Not available, AD: Antidepressant, AED: Antiepileptic drug, AICA: anterior inferior cerebellar artery, MRI: magnetic resonance imaging, BA: Basilar artery, BHS: Bilateral hemifacial spasm, BP: Bell’s paralysis, BTX: Botulinum toxin injections, BZD: Benzodiazepine, CBZ: carbamazepine, C‑dopa: Carbidopamine, CNZ: Clonazepam, CsT: conservative treatment, CT: Computed tomographic, F: Female, HBP: Hypertension blood pressure, HI: Hearing impairment, M: Male, MI: Marked improvement, MS: Multiple sclerosis, MTP: Methylprednisolone, MVD: Microvascular decompression, PICA: Posterior inferior cerebellar artery, SA: Small arteries, SAV: Small arteries and veins, TN: Trigeminal neuralgia, TXP: trihexyphenidyl, VA: Vertebral artery, ~: Mean contractions of short duration.[16,17,19,24,31,55,57,81,92,104] As It is worth noting that the largest series of HFS cases previously reported and as observed here, the hemiface submitted to MVD are Asian, with the exception of the affected second usually presents with less intense series studied by Jannetta’s research group, a US reference spasms.[16,17,19,24,31,57,92] Studies involving MRI and magnetic in MVD. On the other hand, an Asian cohort did not resonance angiogram (MRA) of the brain show that, on show higher prevalence of HFS in relation to other ethnic the hemiface most affected, NVC was more intense.[92] groups.[92] In series studying HFS, there is a low incidence of BHFS Dou et al. (2014)[14] suggested that reduced space in the ranging from 0.0% to 5.7% of cases.[17,19,57,81,92,94] posterior fossa could be involved in the genesis of HFS. This type of anatomical feature increases the likelihood of In our analysis, the mean age of onset of symptoms in neurovascular conflict due to space restriction in this region. BHFS was 58.9 years old, with wide variation between 13 years and 88 years old. The predominance between Secondary causes of HFS are described as 0.0–0.6% of the sexes in 63 cases, for which data were available, cases in published series,[31,34] and include the lesions of was 76% female and 24% male. Symptoms began in the the cerebellopontine angle, schwannoma, meningioma, right hemiface in 36% of these cases and on the left in epidermoid tumor, lipoma, and arachnoid cyst; and 64%. processes in the brain stem, demyelinating diseases, Etiology of hemifacial spasm gliomas, cavernomas, arteriovenous malformations, and strokes.[6,16,24,31,48,80,100,109] Cases of HFS secondary to Paget’s In a 2012 review of 5,685 cases of HFS submitted to disease have also been described.[21,24] MVD, the NVC frequencies most observed were: 37% by AICA (anterior inferior cerebellar artery), 30% by Familial HFS due to probable autosomal transmission PICA, and 23% by multiple vessels.[63] Lee et al. (2016)[53] with low penetration has been reported.[5,7,104] However, studied 2,040 patients submitted to MVD and reported a study of HFS in a family showed that hypertension the frequencies of NVC were: 54.5% by AICA; 27.1% by was the most important factor involved in the genesis of PICA; and 17.1% by multiple vessels. late‑onset spasms.[52] Surgical Neurology International 2017, 8:225 http://www.surgicalneurologyint.com/content/8/1/225

Table 2 (Part III): The 102 cases of bilateral HFS Authors and Felício et al., 2007 Han et al., Yang et al., Kiziltan Lopez‑Castellanos Dou et al., Martins et al., year (location) and 2008 (Brazil) 2009 (Korea) 2009 (Korea) et al., and 2015 and 2016 2016 (Brazil) 2010 (Turkey) Lopez‑Contreras, (China) 2015 (El Salvador) Age at onset 60.7 (average) 50.3 (average) n/a n/a 70.3 (average) 49 50 (years) Sex 5F, 5M 7F 27 ? 3 ? 5F, 1M 8F, 2M 1M % BHS 2.6 0.4 2.3 1.5 2.1 0.7 n/a Etiology Vascular Vascular n/a n/a n/a Vascular Vascular Comorbidity Most of African n/a n/a n/a n/a n/a n/a descendent ‑ 1TN, 1BP,4HBP Side of onset 5 L, 5 R 5 L, 2 R n/a n/a 3 L, 3 R 6L, 4R L Duration/years 6.63 (mean) 8.6 (mean) n/a n/a 12.3 7.8 13 Latency (between 2.8 yrs (mean) 6.1 yrs (mean) n/a n/a 8 yrs 3.8 6 yrs R and L sides) Neuroimaging 1 MRI: 1 dolichoectatic n/a n/a 6 normal n/a L VA tortuosity diagnosis vertebrobasilar L: 1 PICA, 4 and R PICA tortuosity, 4 MRI: AICA, 1 normal normal, 4 CT: normal R: 2 PICA, 3 AICA, 1 normal Therapy 2 BZD, 4 AED, 3 AD, L: 5 MVD n/a n/a 5 BTX, 1 refused 5 MVD CBZ, BTX, 8 BTX R: 3 MVD treatment unilateral and 5 MVD (R and L) MVD bilateral Result n/a n/a n/a n/a 5 slight severity 1MVD unilateral L, R: Transient post BTX 4 MVD unilateral BP, HI (3 bilateral cure and 1 contraleral partial improvement) and 5 MVD bilateral (5 bilateral cure) Follow‑up 100 mos n/a n/a n/a n/a 5-92 mos 17 mos n/a: Not available, AD: Antidepressant, AED: Antiepileptic drug, AICA: Anterior inferior cerebellar artery, MRI: Magnetic resonance imaging, BA: Basilar artery, BHS: Bilateral hemifacial spasm, BP: Bell’s paralysis, BTX: Botulinum toxin injections, BZD: Benzodiazepine, CBZ: Carbamazepine, C‑dopa: Carbidopamine, CNZ: Clonazepam, CsT: Conservative treatment, CT: Computed tomographic, F: Female, HBP: Hypertension blood pressure, HI: Hearing impairment, M: male, MI: Marked improvement, MS: Multiple sclerosis, MTP: Methylprednisolone, MVD: Microvascular decompression, PICA: Posterior inferior cerebellar artery, SA: Small arteries, SAV: Small arteries and veins, TN: Trigeminal neuralgia, TXP: Trihexyphenidyl, VA: Vertebral artery, ~: Mean

The causes of HFS vary, but they are all consequences of with ipsilateral hemiplegia. They suggested that the changes in motor neuron conduction in the nucleus of cause of the facial spasm was associated with changes in the facial nerves by peripheral or central deafferentation the facial nucleus or peripherally in the nerve, rather than and may include cortical and subcortical influences. at the cortical level. A similar case was later described in 1943, in which HFS also did not improve with the Pathophysiology: Historical perspective and onset of ipsilateral hemiplegia subsequent to an ischemic current concepts [17] [36] [61] stroke. In 1909, Hunt proposed that the spasm was In 1890, Gilbert, Cadiot, and Roger (apud Meige, 1907) due to an afferent system resulting from irritation of the described the case of a dog that presented spasms in facial nerve. A hypothesis was proposed that the origin an external ear considered similar to facial spasms in of the spasm could be cortical, but this was contested by humans. Successive resections of the cortex, striatum, Russell (1910)[83] who suggested that spasm discharges and cerebellum were performed with no improvement. originated in the pons of the facial nerve nucleus. However, following unilateral destruction of the facial Babinski (apud Gordon, 1912),[27] expressed the view nerve nucleus, the spasms ceased. that the cause was probably peripheral irritation of the In 1898, Habel et al.[30] described the case of a woman facial nerve. Wilson (1940)[103] suggested that facial nerve with HFS who did not improve after an ischemic stroke stimulation alone rarely produces spasms, but that nerve Surgical Neurology International 2017, 8:225 http://www.surgicalneurologyint.com/content/8/1/225 irritation might result in antidromic conduction to the parallel traveling nerve fibers, lacks funicular structure, nucleus, resulting in abnormal activity that could cause and is less vascularized. The density of the peripheral spasms. segment is greater than the central segment, consisting of undulating nerve fibers, which creates a firmer and more The spread of action potentials in two adjacent elastic structure that is more resistant to compression. unmyelinated axons has been demonstrated in Sensory nerves are usually larger than conduction nerves, experimental studies, by Katz and Schmitt (1940),[43] and consequently the central segments of the latter are later by Arvanitaki (1942),[2] who proposed that the term smaller, providing fewer possibilities for compression.[10] “ephapse.” Granit et al. (1944),[29] demonstrated that This view was supported by Sindou et al. (2002),[89] who “ephapses” occurred in the sciatic nerve of a cat after showed that 54.3% of 579 cases of NVC, using MVD to mechanical compression, which disappeared following treat trigeminal neuralgia, were in the middle portion of its release. Generation of ectopic action potentials the root. A study by Zhong et al. (2012),[108] involving concomitant with ephaptic conduction has also been 1,327 cases of HFS submitted to MVD, showed that demonstrated in spinal motoneurons in dystrophic 93% of NVC occurred in the REZ, 7% occurred in the mice when stimulated antidromically.[35] These ephaptic medial portion of the facial nerve, and none of the cases characteristics are similar to facial spasms, due to NVC presented distal compression by the internal auditory in the REZ, where the transition from oligodendroglia meatus. to Schwann cells occurs.[46,90] Reversibility of abnormal synkinesis after MVD occurs, often within 10 days, in 81% Studies involving intraoperative electromyography (EMG) of the patients who had not been submitted to previous indicated the presence of abnormal muscle peripheral facial nerve block procedures. They correspond responses (AMR) in the facial muscles, such as the to the reversibility of ephapse. The spasm itself might be lateral spread response (LSR), which were attributed to a phenomenon analogous to the ectopic excitation and demyelination/axonal injury of the facial nerve, causing hyperexcitation demonstrated in dystrophic mouse spinal ephaptic transmissions and ectopic excitations, leading to nerve roots.[46] hyperexcitability of facial nucleus motoneurons.[69] In 1962, Gardner and Sava,[25] and later Gardner and Experimental studies in rats have demonstrated that Dohn (1966),[24] reported that myelin lesions due to NVC facial motoneurons are involved in HFS after facial can cause “cross talk” or the spread of action potentials nerve demyelination. It has been suggested that to adjacent axons (transaxonal short‑circuit theory). when a branch of the facial nerve is stimulated, the stimuli are transmitted in axons in both directions, Gardner and Dohn (1966)[24] reported that, in four cases antidromically and orthodromically. They argued that, of HFS refractory to MVD, section of the intermediate to induce facial hyperactivity, the phenomena of facial nerve was performed with complete cessation of spasms nerve demyelination and vascular compression are both and without motor alteration of the facial muscles. required.[51] They suggested that NVC could set up a peripheral reverberating circuit between afferent (proprioceptive) Research has shown that the severity of facial nerve NVC and efferent fibers at the site of compression. is associated with spasm intensity.[88] This fact has been reported previously and thus supports the neurovascular The main cause of HFS is NVC in the REZ, which is cause.[92] more vulnerable because this area is devoid of epineurium and Schwann cells because it is only covered by arachnoid The hypothesis of the peripheral origin of facial spasm cells.[69] These characteristics enable minimal compression suggests that ectopic firing and peripheral ephaptic to result in anatomical changes. Histopathological transmissions that originate in their REZ due to NVC and study of the REZ of facial nerve of patients with HFS demyelination cause hyperexcitability of the facial nerve showed fibers with complete and partial demyelination, nucleus, leading to spasms.[20,69,70] Experimental research with demyelinated axons in contact with each other. has shown that local demyelination induced by the nerve Normal and abnormal fibers showing proliferative injury enables ectopic insertion of Na+ channels, causing hypermyelination with features of microneuromas have hyperexcitable nerve fibers at this level.[79] Demyelination been reported.[82] facilitates close contact between bare axons, promoting direct electrical communication between individual nerve De Ridder et al.[10] suggested that NVC can occur in fibers.[67] any cranial nerve segment within the central nervous system (CNS), not only in REZ or DREZ (dorsal REZ). The hypothesis of the nuclear origin suggests that some They reported that all cranial nerves, except I and II, are form of reorganization of the synapses occurs in the facial composed of a CNS segment and a peripheral nervous nerve nucleus, leading to motor neuron hyperexcitability system segment. The central segment has a structure due to demyelination caused by NVC.[39,64,66,85,98,99] similar to that of white brain matter, it consists of Neurophysiological studies show a high frequency of Surgical Neurology International 2017, 8:225 http://www.surgicalneurologyint.com/content/8/1/225 discharges recorded in muscles innervated by facial nerve foramen. After 4 weeks, EMG monitoring was performed axons, whereas the interference pattern is related to facial on the faces of affected mice that showed AMR waves motor neuron activity or its supranuclear control. This very similar to those monitored during MVDs in HFS. activity is more frequently seen in cases showing longer Electron microscopy showed lesions in the epineurium symptom duration and could be related to the onset of and the tunica adventitia of the vessel. The presence of facial motor neuron hyperexcitability due to antidromic AMRs was only observed in the rats that also presented impulses that results in spontaneous activation.[47] both lesions under microscopic observation. When the vessels were cut and separated from contact with the facial Thus, neither the nuclear nor the peripheral hypotheses nerve, the AMRs disappeared, as occurs during MVD. can be rejected. A study involving EMG in a case of The arteries are covered by adventitia, which contains BHFS, with asynchronous contractions in each hemiface the vasa vasorum and the autonomic nerve endings and treated unilaterally, showed complete resolution of that release neurotransmitters. These neurotransmitters ipsilateral spasms and the persistence of spasms on the act in neuromuscular junctions and control vessel contralateral side. This finding suggest independent expansion and contraction. Once the cervical sympathetic trigger mechanisms in both hemifaces, more likely due ganglia ipsilateral to the NVC were removed, the AMRs to bilateral nerve zone irritation by aberrant vessels than disappeared.[51] These findings indicate that an effective hyperexcitability of a facial nerve nucleus spreading to the participation of the sympathetic innervation occurs in contralateral side.[86] Similarly, another electrophysiological the pathogenesis of HFS, possibly through the release study demonstrated asynchrony, asymmetry and of norepinephrine. The authors suggested that while the differences in the patterns of spasm activity in each adventitia is wearing out, particularly during moments hemiface in cases of BHFS.[47] Most cases of bilateral when sympathetic impulses occur, neurotransmitters BHFS not improve bilaterally following unilateral MVD, released from sympathetic endings may spillover from as observed in our case. These observations suggest that the breakage and spread to nerve VII fibers in close there is no interrelationship between the facial nerve contact with the offending arteries. Thus, after removing nuclei. Following treatment with BTX‑A in patients with the compressor artery and in the absence of AMRs, HFS, decreases in the synkinetic response of the blink they dripped norepinephrine on the nerve where the reflex and AMR were observed, suggesting that skin or compression occurred and the AMRs reappeared. They muscle afferent volleys via the trigeminal nerve enhance concluded that sympathetic innervation was involved, the excitability of facial nerve motor neurons in HFS.[75] via neurotransmitters, in the pathogenesis of HFS. They Spasm‑induced somatosensory input from the skin may also speculated regarding the possibility of Na+ channel activate the somatosensory afferent pathway and basal involvement in the genesis of action potentials generated ganglia‑thalamo‑cortical motor circuits.[26] Activation of in facial nerve axons and concluded the study by the thalamus is probably due to projections arising from stating that more work is required to substantiate the muscle spindles, as demonstrated in an experimental “sympathetic hypothesis.”[15] It is important to highlight study on rats.[42] Brain circuitry may be altered in patients that this hypothesis does not explain cases of HFS with HFS, as Tan et al. (2004)[92] have suggested. secondary to cysts, to extrinsic and intrinsic brainstem, A thought‑provoking study[15] showed that once the cerebellum, and fourth ventricle tumors, and particularly offending artery was intraoperatively removed from the in demyelinating and ischemic diseases. nerve, the AMR wave diminished immediately and most A study involving positron emission tomography (PET muscle spasms improved following MVD treatment for scan) in patients with HFS compared with asymptomatic HFS. This cannot be easily explained by the combined controls showed bilateral glucose hypermetabolism in the peripheral and nuclear hypotheses, since insufficient time somatosensory thalamus [corresponding to the ventral had passed for histological repairs in the area of NVC. posteromedial (VPM) nucleus, related to the sensory Thus, Dou et al. (2015)[15] proposed a new explanation somatotopic part of the face] in patients with HFS, in for the pathogenesis of spasms in which the offending both active and suppressive states. It is worth noting that artery played a more important role than the mere effect the upper part of the face receives motor afferents from of mechanical compression in the pathogenesis of the ipsilateral and contralateral facial nerves. The spasms were HFS. They suggested that attrition at the neurovascular significantly reduced following suppression with BTX‑A, interface is the essence of HFS etiology and that the according to the Jankovic disability rating scale. Thalamic substance of the disease is emersion of ectopic action hypermetabolism was attributed to various causes, such potentials from the demyelinated facial nerve fibers, as skin afferents and neuromuscular spindles, antidromic which are trigged by sympathetic endings from the conduction of the facial nerve and secondary changes in offending artery wall. In support of this hypothesis, they the CNS.[88] repeated the Kuroki and Møller (1994)[51] experiments in mice, in which the superficial temporal artery was place in It has been reported that in patients with unilateral contact with the facial nerve where it exits in stylomastoid writer’s cramp, functional MRI (f‑MRI) showed increased Surgical Neurology International 2017, 8:225 http://www.surgicalneurologyint.com/content/8/1/225 activity in both putamens, the caudate nuclei, the The study of transcranial magnetic stimulation (TMS) internal globus pallidus, and the thalamus during tactile showed cortical influence on HFS, which, through stimulation of the right index finger. During dystonias, cortical mechanisms, such as postexcitatory inhibition the basal ganglia‑thalamo‑cortical motor circuit can of motoneurons after excitation of the corticonuclear occasionally be bilaterally activated by hemilateral tract, may activate the corticonuclear inhibitory stimuli. Blepharospasm and HFS seem to show similar system controlled by intracortical mechanisms pathophysiology, which explains the bilateral activation modulated by basal and thalamus ganglia. The facial of the thalamus by a unilateral stimulus.[78] It has motoneurons respond easily to trigeminal stimulation, been suggested that after BTX‑A application in HFS, they presumably receive only mild or short‑lasting sensory afferents of the neuromuscular spindles via the excitation of the corticobulbar inhibitory descending trigeminal nerve to the thalamus can diminish, which projections.[50] would partially explain the small reduction in thalamic Considering the data outlined here, we argue that hypermetabolism on a PET scan. It is possible that other sensory afferents via nerve VII remain. Hypermetabolism the most probable explanation is ectopic firing and in the cerebellum was also observed, which could be ephaptic transmissions, originating in the REZ of the due to facial muscle activity. No hypermetabolism was facial nerve due to NVC, orthodromically stimulate the observed in the primary (M1) motor area.[88] Sensitive facial muscles and antidromically stimulate the facial afferents arising from the intermediate nerve conducted nerve nucleus, while the latter, in its hyperexcited state, to the spinal nucleus of the trigeminal nerve could also also intermittently stimulates the facial muscles. These remain, which drive to the sensory thalamus and then to activated muscles trigger the somatosensory afferent the cortical somesthetic area. impulses of the skin and neuromuscular spindles of the face conducted by the trigeminal nerve, which after As mentioned above, Gardner and passing through the gasserian ganglion and trigeminal [24] Dohn (1966) described four patients with HFS who nuclei, reach the contralateral VPM somatosensory showed no improvement following MVD, who were then thalamic nucleus, which then drive to the cortical submitted to intermediate nerve section, with complete somesthetic area of the face. cessation of the spasms. Thus, sensory fibers of the intermediate nerve come from the outer ear, part of the Once activated, this area stimulates the primary and external auditory meatus, and outside of the eardrum. supplementary motor areas through the extrapyramidal Central extensions of ganglion cells geniculated to the system, while the basal ganglia retrogradely activate peripheral sensitivities enter the brain stem through the the motor neurons of the facial nerve nucleus, which nerve and drive to the spinal nucleus of the trigeminal peripherally stimulates the facial muscles. In addition, the nerve. Peripheral extensions of sensory neurons located in intermediate nerve, which is anatomically aligned with the gasserian ganglion and the mesencephalic trigeminal the facial nerve, likely participates in this pathophysiology. nucleus receive peripheral impulses from the face Its impulses orthodromically drive to the spinal trigeminal sensitivity of the face and, together with the sensory fibers nucleus and ascend to the basal ganglia‑thalamocortical of the intermediate nerve, drive to the sensory trigeminal circuits, whereby descending feedback activates the nucleus. After connecting with secondary neurons in the facial nerve nucleus, expressed peripherally through brainstem (except neurons of the mesencephalic nucleus spasms [Figure 1, Adapted from Afifi and Bergman[1] and of the trigeminal nerve, which contains primary neurons Obeso, Rodriguez and DeLong[74]]. like the gasserian ganglion), most of the fibers cross the It is worth emphasizing that the patient cannot suppress midline driving to the VPM nucleus of the thalamus and the spasms voluntarily and that they persist during after connecting to these neurons, reach sensory cortical sleep and anesthesia, a fact verified in this case, clearly areas, which are connected with motor areas that in indicating the influence of the extrapyramidal system and turn are modulated by the basal ganglia, thalamus, and the basal ganglia. cerebellum.[1,45,74] It is possible that the intermediate nerve, also compressed in the DREZ by the vessel, is Patients with central facial paralysis, who cannot involved in the genesis of HFS. voluntarily move the muscles of the lower face, show involuntarily movement through reflexes, in response There are connections between the trigeminal nerve to emotional stimuli from the basal ganglia to the and the facial nerve, which can be demonstrated by the facial nerve nuclei.[1] Clinical observations have shown blinking reflex in response to stimulus in the cornea.[1] that emotional factors, such as stress, influence the Research has shown the activation of primary and precipitation or exacerbation of HFS.[95] This suggests the supplementary motor areas by evoked potentials during influence of the cognitive/associative and limbic systems voluntary eyelid movement,[91] but this has yet to be on the basal ganglia and the extrapyramidal system in verified for involuntary movements. HFS [Figure 1, Adapted from Afifi and Bergman[1] and Surgical Neurology International 2017, 8:225 http://www.surgicalneurologyint.com/content/8/1/225

Figure 1: Simplified scheme of motor, sensory, cognitive/associative and limbic systems

Obeso, Rodriguez and DeLong[74]] Further investigation by Barker et al. (1995).[6] One report describes a case should clarify these suppositions. of bilateral synchronous HFS following bilateral Bell’s palsy.[101] In a North American series of 293 HFS cases, Clinical presentation 22.8% had moderate to severe facial motor deficits Although HFS is not life‑threatening, it can cause (≥III House and Brackmann), principally among those major disruptions to daily life activities such as driving submitted to BTX‑A.[97] In our case, Bell’s palsy did not and working, causing withdrawal from socializing and occur before the onset of the spasms. even depressive disorders.[63,93] The natural history of the disease begins with irregular twitching and clonic Previous auditory deficit is also not uncommon in HFS and tonic contractions in the lower part of the orbicular patients submitted to MVD. Huang et al. (1992)[34] verified oculi muscle, until it encompasses the entire muscle. It auditory deficit in 4.8% of 310 cases, while Thirumala progresses to the lower part of the same hemiface and can et al. (2011)[97] reported it in 12.3% of 293 cases. In manifest in the platysma muscle.[15‑17,19,34,47,63,84,94,97,100,104] a series of 143 HFS cases submitted to MVD, 41% presented abnormalities in the middle ear acoustic reflex Contractions may progress, with predominance of the in the preoperative period, suggesting that NVC can affect tonic component over the clonic.[57,94,97] Atypical HFS both the acoustic and facial nerves. In the same series, is characterized by onset in the orbicularis oris muscle 2.8% of cases presented significant postoperative auditory and buccinator, which may ascend to the orbicular oculi deficits.[68] In a series of 34 patients with HFS submitted muscle.[6,84,87,97] Spasms worsen with stress and fatigue, to MVD, 17.6% presented auditory deficits ipsilateral to they cannot be suppressed voluntarily, and they persist the HFS, and 2.9% had severe dizziness.[77] Our patient during sleep or anesthesia. presented mild to moderate bilateral auditory deficits. The spasms begin in adult life, around 45 years of age, Differential diagnosis and prior history of peripheral facial paralysis or traumatic A diagnosis of BHFS requires considerable care, since it nerve injury is not uncommon.[6,16,17,24,44,55,72] In a large series, can be mistaken for other facial dyskinesias: motor nerve dysfunction was verified in 57% of cases.[6] • Blepharospasm consists of symmetrical, synchronous, Synkinesis has been reported in 70% of cases with HFS.[47] and bilateral contractions of the orbicularis oculi Mild facial motor deficit has also been observed, with 10.3% muscle, and may be associated with contractions of of patients affected in an Asian series of 310 cases.[34] the frontalis muscles and the corrugator and procerus Voluntary movements of the face and speech can worsen muscles, resulting in characteristic depression of the spasms.[24,28,102] Some patients complain of “clicks” in the eyebrows (Charcot’s sign).[44] There is no evidence ipsilateral ear due to contraction of the stapedius muscle, of the Babinski‑2 sign, present in the HFS, which and auditory deficit may be observed.[17,24,34,46,68,80,97] is characterized by unilateral contraction of the The ipsilateral facial paralysis preceded 1.9% of 106 cases frontalis muscle, causing eyebrow elevation, with of HFS studied by Ehni and Woltman (1945),[17] simultaneous contraction of the ipsilateral orbicularis 15.3% of 131 cases studied by López‑Castellanos and oculi muscle, resulting in eyelid closure[12,56,104] Lopez‑Contreras (2015),[56] and 2% of 648 cases studied • Facial tics usually begin in childhood, though their Surgical Neurology International 2017, 8:225 http://www.surgicalneurologyint.com/content/8/1/225

characteristics can change, they can be controlled an expansive lesion at the cerebellopontine angle. A lack voluntarily and they do not improve with rest. of visible neurovascular conflict is often due to limitations Besides the facial nerve, other nerve groups may be in the imaging method.[92] The studies comparing specific involved, a finding observed in younger patients. sequences of MRI imaging acquisition improved surgical The movements are abrupt and multifocal. They are planning for patients with NVC. There was a diagnostic associated with motor, phonic, gestural tics, or other correspondence in the evaluation of 1.5 T with T2 fast signs and symptoms of Tourette’s syndrome[55,57,94] spin echo and intraoperative findings.[96] Garcia et al. • Facial myokymia is characterized by unilateral and demonstrated that there is a higher resolution and temporary contraction of the orbicularis oculi muscle, greater sensitivity with 3D‑CISS and 3D‑TOF MRA at usually associated with periods of physical or emotional 3 T compared with 1.5 T in patients with NVC.[23] The stress, fatigue, or excessive caffeine consumption[49,94,104] high‑resolution STIR MRI sequence can be considered a • Synkinesis following facial nerve paralysis leads to good method for simultaneous evaluation of vessels and the activation of several muscles innervated by the cranial nerves, even without contrast.[32] facial nerve and it typically occurs in the context of EMG is characterized by discharge patterns of spasm voluntary movement[49,94,104] activities that can occur as single isolated, clustered, and • Oromandibular dystonia is usually bilateral and tonic spasms. Isolated discharges are more prevalent in affects other muscular groups not innervated by the patients with HFS with shorter disease duration, though facial nerve, such as the pterygoid, masseter, and over time, tonic spasms tend to prevail. In patients with temporalis muscles[104] BHFS, the spasms are asynchronous and asymmetric and • Hemimasticatory spasm affects the musculature the patterns of spasms activities are different.[47] involved with the trigeminal nerve with painful contraction of the medial pterygoid, masseter, and Audiometry should be performed to ensure pre‑ and temporalis muscles[49,94,104] postoperative comparisons.[37] • Psychogenic facial spasm does not present a specific pattern of contractions, intensity, and frequency. It Treatment To treat HFS, oral medication, BTX‑A, and MVD have can involve muscles not related to the facial nerve all been described. Treatment with oral medications is and can be modified by distraction generally considered unsatisfactory. The most commonly • Drug‑induced late‑onset dyskinesias, mainly by prescribed drugs are carbamazepine, phenytoin, neuroleptics, manifest as stereotypical orofacial, clonazepam, baclofen, and gabapentin.[6,19,57,63,80,94,97,109] lingual and limb movements, and akathisia[19,94,104] • Focal seizures characterized by rapid clonic contractions Acupuncture was prescribed for 85 patients in a series of that can be observed in an EEG or an EEG video.[17] 310 cases and for 65 patients in another series of 545 cases with HFS, but showed no therapeutic benefits.[34,54] The long latency period that occurs between the onset of HFS and contralateral involvement is symptomatic and BTX‑A applications are a practical therapy that has assists in the differential diagnosis of BHFS and other low morbidity and good clinical response. In general, movement disorders.[19,31,33,94] EMG studies may assist in BTX‑A is injected into the affected muscles, resulting the diagnosis of HFS.[13,55,68,94] in presynaptic blockade of the motor plate that provides Comorbidities a good therapeutic response. The patient remains free from symptoms for 3–4 months, after which it must be Arterial hypertension (AH) is the main HFS‑related reapplied.[19,55,57,76,93,94,106] The most frequent complications comorbidity, occurring in 24% of cases in a series associated with this treatment are peripheral facial of 648 patients, and 18.9% in another series of paralysis, diplopia, and palpebral ptosis. However, 587 patients.[6,8] Besides AH, the increase in patient age after prolonged use, the efficacy of the neurotoxin can was related to hyperactive dysfunction syndrome (HDS), diminish or fail, resulting in an unsatisfactory response.[80] when an increase in the atherosclerotic process occurs together with AH, which leads to vessel stretching and This treatment is the first option in patients with tortuosity. This can result in compression of the DREZ high anesthetic risk, who present milder or refractory or REZ of the nerves. AH generally precedes HFS.[11] symptoms or in those who present HFS relapse following MVD. In cases of BHFS after unilateral MVD, in which Gardner and Dohn (1966)[24] described a case of BHFS hearing loss is a complication, the use of contralateral secondary to Paget’s disease with basilar impression. BTX‑A is an excellent option to avoid the risk of bilateral BHFS associated with blepharospasm and associated with hearing loss, which has high morbidity. Wang and cervical dystonia have both been reported.[44,92] Jankovic (1998)[102] published the first case of a patient Complementary examinations with painful tic convulsif (HFS + trigeminal neuralgia) MRA and MRI are important for evaluating neurovascular who showed improvement in both symptoms following conflicts, observed in 15% of HFS cases, or the presence of BTX‑A application. A similar case was published in Surgical Neurology International 2017, 8:225 http://www.surgicalneurologyint.com/content/8/1/225

2002.[62] BHFS and unilateral painful tic convulsive has may be considered for surgical re‑exploration.[38] also been described, in which the spasms and ipsilateral Persistence of motor neuron hyperactivity of the facial trigeminal neuralgia improved following the application nerve nucleus was demonstrated in the postoperative of BTX‑A.[18] period by electrophysiology studies, which explains the persistence of spasms for a certain period.[40] The best long‑term therapeutic response for HFS Microanatomical changes, such as demyelination, due to NVC is endoscope[9,58] or microscope‑assisted MVD.[6,34,49,54,60,63,72,107,109] MVD is the only option for myelin sheath vacuolization, and partial axonal curing HFS.[49,63,109] Improvement in the spasms can degeneration, caused by NVC were also demonstrated occur immediately following MVD or may take several by microscopy. Electrophysiological changes, such as months.[25] changes in F waves and AMR that are indicative of neuronal excitability, have also been described.[41,69‑71,82] Intraoperative EMG monitoring has shown the immediate disappearance of AMR or LSR recorded from a muscle The mechanism of spasm improvement depends on two innervated by the superior branch of facial nerve when factors. The primary mechanism is due to the interruption the inferior branch was stimulated, or conversely, during of ectopic excitation and the efficient transmission that MVD. This phenomenon is probably due to ephaptic occurs following REZ decompression, leading to the transmission at the lesion site or in combination with abrupt disappearance of the spasms, in most cases. The motor nucleus hyperactivity.[65] It has been suggested secondary mechanism is due to remyelination of the that the disappearance of LSR is a good predictor for affected segment, with the disappearance of LSR, and obtaining an optimal result,[37,87,97,108] and two large perhaps the gradual decrease of neuronal hyperexcitability studies involving thousands of patients show that AMR in the facial nucleus, which could explain delayed [22,38,40,69‑71,97] vanished after MVD in 93.9% of HFS cases.[107,108] Some improvement. authors recommend intraoperative EMG, since this form The persistence of spasms in the immediate postoperative of monitoring is very useful when manipulating the facial period varies widely in the literature: 50.3% (Ishikawa [37,65,97,108,109] nerve, to avoid deficits. et al., 2001),[38] 34% (Marneffe et al., 2003),[59] [34] [46] One study reported that direct stimulation of the 12% (Huang et al.), 5.8% (Kim et al.). Most residual [22,38,54,59] offending artery during surgery in cases of HFS spasms improve in up to a year. produces a wave analogous to AMR, denominated the Intraoperative brainstem auditory evoked “Z‑L response,” which disappeared immediately after potential (BAEP) monitoring helps prevent auditory decompression. Monitoring the Z‑L response is useful deficit.[37,60,84,97] when an AMR is not recorded prior to decompression or if it persists after all vascular compressions are properly In 2012, a systematic review of 5,685 HFS cases treated. It can help determine the real culprit when submitted to MVD verified complete cessation of multiple offending vessels exist.[109] spasms in 91.1% of the cases. The mean follow‑up was 2.9 years. Spasms recurred in 2.4% of patients The duration until complete cure of HFS after MVD and 1.2% were submitted to a second MVD. Transient was studied in 175 Japanese patients, who were assigned complications included 9.5% facial deficit, 3.2% auditory to two postoperative groups: Group I (n = 88), deficit, and 1.4% cerebrospinal fluid fistula. Permanent in which the residual spasms resumed on day 4, complications included 2.3% auditory deficit, 0.9% facial after a period of silence, and diminished gradually paralysis, 0.06% stroke, and 0.02% death. Curiously, the until complete resolution in 28 days, on average; second author of this article had HFS for 5 years, which and group II (n = 87), in which the spasms ceased was cured with MVD.[63] immediately after surgery. In group I, 10 (11%) patients did not present a period of silence. Complete resolution Treatment of HFS by MVD is curative in approximately of the spasms took more than a year in six (7%) 90% of cases in the long term and is therefore the best group I patients, with two patients presenting long definitive treatment. Improvement immediately following delays, one of 22 months and another of 27 months. surgery was observed in 76.7% of cases, on average, with Facial paresis is common in the postoperative period, the majority of delayed improvements resolving within however, no case of permanent facial paralysis was a year. Partial improvement varied from 1.3% to 9% observed. The authors concluded that approximately and the total failure of MVD ranged from 2.6% to 9%. 50% of patients show persistent postoperative Cases of recurrence ranged from 1% to 3.2% in follow‑up spasms after a 4‑day period of silence, with complete ranging from 1 year to 18 years. Permanent hearing loss resolution occurring in 25% of cases in 1 week, 50% ranged from 1.1% to 2.9% and permanent facial deficit in 1 month, and 90% within 8 months postsurgery. ranged from 0.7% to 2.9% of cases. There was only one If the spasms do recur after 4 days and there is no case (0.01%) of mortality due to infection in 8,096 cases facial paresis, recurrence is more likely and the patient of HFS submitted to MVD [Table 3]. Surgical Neurology International 2017, 8:225 http://www.surgicalneurologyint.com/content/8/1/225

Table 3 (Part I): Results and complications (%) of MVD treatment of HFS Authors Number Immediate Delayed Partial Full Did not Recurrence Permanent Permanent Follow‑up/ Notes and year of MVD cure cure improvement recovery improve facial auditory years (location weakness damage Niemeyer 53 81.1 18.9 ‑ 91 ‑ ‑ ‑ ‑ ‑ ‑ Filho, Bezerra 7 d – 16 mos and Mufarrej, 1990 (Rio de Janeiro, Brazil) Huang et al., 310 88 5.2 ‑ 93.2 ‑ 1 ‑ ‑ ‑ ‑ 1992 (Taipei, Up to 22 mos Taiwan) Barker 648 86 ‑ 7 84 9 2 0.9 2.6 10 ‑ et al., 1995 (Pittsburgh, USA) Zhang 300 ‑ ‑ 1.3 92 3.4 3 1 2.0 ‑ 3% controlled et al., 1995 Up to 5 yrs 1.0 tinnitus infection (Guangzhou, 0.3 death by China) infection Payner and 34 ‑ ‑ 9 85 6 ‑ 2.9 2.9 6.2 ‑ Tew, 1996 (Cincinnati, USA) Rothon, 72 ‑ ‑ 7 87 6 Majority 1.4 2.8 1‑18 In: comments 1996* (USA) <1 yr Payner and Tew, 1996 Ishikawa 175 49.7 * ‑ ‑ ‑ ‑ ‑ ‑ ‑ 50.3 cases, et al., 2001 spasms (Saitama, began again Japan) on 4th d and diminished in up to 28 d. Improvement >1 yr in 7% Samii 143 59 ‑ ‑ 90.6 ‑ ‑ ‑ ‑ 9.6 ‑ et al., 2002 (Hannover, Germany) Li, 2005 545 87.9 After 3 mos: ‑ 93.4 ‑ ‑ ‑ ‑ ‑ 1 case took (Taipei, 91.4 2 yrs to Taiwan) After 6 mos: improve 93.4 ~: Mean, *comments

Special secondary cases of HFS can be treated with was resolved with bilateral surgery. Microvascular other techniques such as embolization, when treating decompression is a definitive, long‑term surgical option arteriovenous malformations, gamma knife surgery, or with low complications. [31,34,48] microsurgery. All of these methods are effective. In In cases of BHFS, we believe that the best approach is cases of HFS associated with Paget’s disease, the use of bilateral MVD. If hearing loss occurs following a unilateral [21] alendronate sodium may be favorable. surgery, the use of contralateral BTX‑A is the best option to avoid the risk of bilateral hearing loss, a complication CONCLUSIONS of considerable morbidity. Use of BTX‑A prior to other treatments should be considered in patients with a high BHFS is a rare neurological syndrome. Diagnosis is anesthetic risk, when the symptoms in one hemiface are a challenge that depends on excluding other facial mild, to avoid surgery on that side, or at the patient’s dyskinesias. We present the tenth case of BHFS, which discretion. Surgical Neurology International 2017, 8:225 http://www.surgicalneurologyint.com/content/8/1/225

Table 3 (Part II): Results and complications (%) of MVD treatment of HFS Authors Number Immediate Delayed Partial Full Did not Recurrence Permanent Permanent Follow‑up/ Notes and year of MVD cure cure improvement recovery improve facial auditory years (location weakness damage Yuan et al., 1,200 ‑ ‑ 5.6 88 2.6 3.2 ‑ ‑ >1 to >6 ‑ 2005 (Beijing, China) Han et al., 1,642 ‑ ‑ 5.9 87.7 ‑ 0.8>6 mos 1.3 2.2 ‑ 1.1 stroke or 2009 Improved hemorrhage (Sungnam, >90% 3.9 infections Korea) 1.3 CSF leak Chang et al., 587 75.1 24.9 showed ‑ ‑ ‑ 3.1 ‑ ‑ ‑ Probability of 2012 (Seoul, progressive Mean of recurrence Korea) improvement 32.9 mos 1% in 1 yr, 1.7% in 2 yrs and 2% in 5 yrs Sindou,* 180 76 34% from 3 ‑ ‑ ‑ ‑ ‑ ‑ ‑ ‑ 2010 (France) mos to 1 yr Marneffe 2 cases up et al., 2003 to 3 yrs (France) Hyun et al., 1,174 ‑ Improved up ‑ 94.1 5.9 ‑ 0.7 1.1 ‑ 0.25 CSF 2010 (Seoul, to 12 mos leak, 0.17 Korea) stroke/ hemorrhage Thirumala 293 88 ‑ ‑ 92.3 ‑ ‑ ‑ ‑ 4.5 ‑ et al., 2011 (Pittsburgh, USA) Zhong 1,327 ‑ ‑ 5.5 90.5 4 ‑ ‑ ‑ ‑ Reoperation et al., 2012 in 5.7% with (Shanghai, cure in 90% China) Total mean/ 8,096 ~ 76.7 ‑ 1.3 – 9 ~ 89.9 2.6 – 9 1 – 3.2 0.7 – 2.9 1.1 – 2.9 1‑18 ‑ band Miller and 5,685 72.8 ‑ ‑ 91.1 ‑ 2.4 0.9 2.3 2.9 1.2 Miller, 2012 reoperation (North 0.06% stroke Carolina, 0.02% death USA) Systematic Review CSF: Cerebrospinal fluid, ~: Mean. *comments.

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